Altered Expression Of CD44 Research Articles

CD44 related stemness maneuvers oral squamous cell carcinoma biology.

Despite the commendable advancements in oral squamous cell carcinoma (OSCC) diagnostics and therapeutics, it remains a considerable medical challenge. Recent evidence suggests that small populations of stem-like cancer cells are responsible for tumor initiation, progression and metastasis. These cancer stem cells (CSCs) have been identified and characterized in various types of cancers, including OSCCs. CSC hypothesis has been supported by the expression of CD44, CD133, ALDH1 and ABCG2. Amongst them, CD44 (a transmembrane glycoprotein), is the most reported CSC marker in OSCCs. The increasing incidence of OSCC combined with its poor survival rates motivates a need for research into the expression of adhesion molecules and may play a pivotal role in studying tumor biology related to invasion and distant metastasis. To quantify the expression of CD44 in the different grades of OSCC and to correlate the expression of CD44 with clinicopathological parameters. A total of 20 formalin-fixed paraffin-embedded tissues of OSCC were retrieved from department archives. Immunohistochemical staining was performed using anti-CD44 antibody (Biogenex). The expression was assessed semi-quantitatively in varying histopathological grades of OSCC and were correlated with tumor, node, metastasis (TNM) staging which were obtained from the department records. The results were statistically evaluated. Overexpression of CD44 was detected in 48% of well-differentiated OSCCs followed by a linear decrease in moderately differentiated and poorly differentiated OSCCs and the expression correlated with the tumor size (T) in 23% cases and with lymph node metastases (N) in 42% of cases (P ≤0.05). The results of the present study suggested an altered expression of CD44 in OSCC. This depicts an association of CD44 with tumor aggressiveness and Epithelial Mesenchymal Transition (EMT) related to loss of cell adhesion in a subset of OSCC-clearly stating tumor cell stemness as a key factor in malignant potential of OSCC.

Altered Expression of CD44, SIRT1, CXCR4, miR-21, miR-34a, and miR-451 Genes in MKN-45 Cell Line After Docetaxel Treatment.

Today it is known that the gene expression profile of cancer stem cells differs from other cancer cells, which may lead to the resistance to routine treatments. The aim of this study was to investigate the effect of docetaxel (DOC) treatment on CD44+ cell frequency in human gastric cancer (GC) MKN-45 cell line and its effect on expression levels of SIRT1, CXCR4, microRNA (miR)-21, miR-451, and miR-34a that are closely correlated with the chemoresistance or self-renewal of cancer stem cells (CSCs). The cytotoxic effect of DOC on MKN-45 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-assay. The frequency of CD44+ cells was measured by flow cytometry in the treated and control groups. The expression level of SIRT1, CXCR4, miR-21, miR-451, and miR-34a was assessed in DOC-treated and non-treated cells using quantitative real-time PCR. Data were analyzed using Statistical Package for the Social Sciences (SPSS) software. The half-maximal inhibitory concentration (IC50) of DOC was 10μg/ml after 48h. Flow cytometry showed a significant increase in CD44+ cells after treatment with DOC (94.3%) when compared with non-treated cells (84.6%) (P < 0.01). The expression of SIRT1, CXCR4, and miR-21 was up-regulated (1.4-fold, 6.7-fold, and 1.22-fold, respectively, P < 0.05) in DOC-treated cells relative to non-treated cells, while miR-451 and miR-34a were down-regulated (0.14-fold and 0.36-fold, respectively, P < 0.05). DOC treatment affected CD44+ cell frequency in MKN-45 cell line and induced significant changes in the expression of SIRT1, CXCR4, miR-21, miR-451, and miR-34a that are implicated in stemness and chemo-radioresistance, which might offer new insights for future GC therapies.

A study on the expression of CD44 adhesion molecule in oral squamous cell carcinoma and its correlation with tumor histological grading

Background: The increasing incidence of oral squamous cell carcinoma (OSCC) combined with its poor and unchanged prognosis motivates a need for research into the aspects of tumor biology such as the expression of adhesion molecules. Alterations in the properties of adhesion molecules could play a pivotal role in the development and progression of invasive cancer and distant metastasis. Aim: This study aims to quantify the expression of cluster of differentiation 44 (CD44) in the different grades of OSCC. Materials and Methods: Immunohistochemical staining for CD44 was performed in 10 tissue sections each of normal mucosa, well-differentiated OSCC, moderately differentiated OSCC, and poorly differentiated OSCC. CD44 positivity was analyzed quantitatively in 10 representative fields of each section under 20× magnification. Statistical Analysis Used: Statistical analysis was performed using Statistical Package for Social Sciences software, version 20.0 (SPSS Inc., Chicago, IL, United States). Results: The mean value of the number of positive cells in controls was 745 ± 68.17, in well-differentiated OSCC was 694.2 ± 145.47, in moderately differentiated OSCC was 349 ± 78.40, and in poorly differentiated OSCC was 108.8 ± 34.39. Conclusion: The results of this study suggest an altered expression of CD44 in OSCC with weak immunostaining in poorly differentiated squamous cell carcinoma. Thus, it can be inferred that the loss of cell adhesion, correlated to the decrease of CD44 expression, might be of value in determining the progression of OSCC.

409 Inhibition of Fatty Acid Synthase Reduces Metastasis in Colorectal Cancer via Altered Expression of CD44 and Disruption of the Signaling Network Downstream of the CD44/C-MET Complex

409 Inhibition of Fatty Acid Synthase Reduces Metastasis in Colorectal Cancer via Altered Expression of CD44 and Disruption of the Signaling Network Downstream of the CD44/C-MET Complex

CD44 in hematological neoplasias

The CD44 protein family spans a large group of transmembrane glycoproteins acquired by alternative splicing and post-translational modifications. The great heterogeneity in molecular structure is reflected in its various important functions: CD44 mediates (1) interaction between cell and extracellular matrix, (2) signal submission, e.g., by acting as co-receptor for membrane-spanning receptor tyrosine kinases or by association with intracellular molecules initiating several signaling pathways, and (3) anchor function connecting to the cytoskeleton via the ezrin-radixin-moesin protein family. The expression pattern of the different CD44 isoforms display strong variations dependent on cell type, state of activation, and differentiation stage. In hematopoietic cells, CD44 mediates interaction of progenitor cells and bone marrow stroma during hematopoiesis, regulates maturation, and activation-induced cell death in T cells, influences neutrophil and macrophage migration as well as cytokine production, and participates in lymphocyte extravasation and migration. CD44 is involved in development and progress of hematological neoplasias by enhancement of apoptotic resistance, invasiveness, as well as regulation of bone marrow homing, and mobilization of leukemia-initiating cells into the peripheral blood. Thereby altered CD44 expression functions as marker for worse prognosis in most hematological malignancies. Additionally, CD44 expression levels can be used to distinguish between different hematological neoplasias and subtypes. Concerning new treatment strategies, CD44 displays promising potential either by direct targeting of CD44 expressed on the malignant cells or reversing an acquired resistance to primary treatment mediated through altered CD44 expression. The former can be achieved by antibody or hyaluronan-based immunotherapy.

Obstructive Jaundice Alters CD44 Expression in Rat Small Intestine

Hypothesis: CD44 is an adhesion molecule expressed by neutrophils, lymphocytes and epithelial cells. CD44 is involved in cell-cell and cell-matrix binding. In addition to lymphocyte trafficking, CD44 also plays a crucial role in the maintenance of intestinal villus integrity. We hypothesize that obstructive jaundice may alter CD44 expression in the rat small intestine and oral glutamine intake can restore the altered CD44 expression in the small intestine of the rat undergoing obstructive jaundice. Materials and Methods: In a prospective animal model study at a university hospital, 41 Sprague-Dawley rats were randomized to 4 groups. Group A (n = 13, control) underwent a sham operation. Group B (n = 12, obstructive jaundice for 1 week) underwent common bile duct ligation. Group C (n = 8, obstructive jaundice for 2 weeks) underwent common bile duct ligation. Group D (n = 8, obstructive jaundice for 2 weeks) underwent common bile duct ligation with oral glutamine intake daily. After 1 and 2 weeks, segments of the proximal jejunum and distal ileum were harvested from groups A and B and groups C and D, respectively. Immunohistochemical expression of CD44 on the cell surface was then evaluated and recorded. Comparisons among the 4 groups were performed. Results: In the 1-week obstructive jaundice group, 173.8 ± 24.0 cells/1,000 enterocytes of the proximal jejunum expressed surface CD44, while 137.0 ± 13.8 cells were stained in the control group (p < 0.001). In the 1-week obstructive jaundice group, 169.8 ± 20.7 cells/1,000 enterocytes of the distal ileum expressed surface CD44, while 119.5 ± 20.8 cells were stained in the control group (p < 0.001). In the 2-week obstructive jaundice group, the number of cells expressing surface CD44 were significantly decreased both in jejunum (112.1 ± 17.0, p = 0.002) and ileum (100.1 ± 12.5, p = 0.028) when compared with those of the control group. With daily oral glutamine intake in group D, the number of cells expressing surface CD44 in the jejunum (149.3 ± 29.7) was restored to that of the control group (p = 0.302) and the number of cells expressing surface CD44 in the ileum (140.4 ± 23.0) was even higher than that of the control group (p = 0.045). Conclusion: Obstructive jaundice for 1 week initially upgraded CD44 expression in the rat small intestine and the CD44 expression later became significantly depressed after obstructive jaundice for 2 weeks. Oral glutamine intake daily could effectively restore the CD44 expression in the small intestine of the rat undergoing obstructive jaundice for 2 weeks.

Altered Expression of CD44 and Variant Isoforms in Human Adenocarcinoma of the Endocervix during Progression

Objective. Altered expression of the CD44 family of cell adhesion molecules has been associated with tumor progression and metastasis. The aim of this study was to investigate the expression of the gene products of CD44 standard (CD44s) and several alternatively spliced variants (CD44v4, v6, v7, and v9) in adenocarcinoma of the endocervix and to correlate the degree of their expression with disease progression.Methods. Immunohistochemical staining for CD44s and CD44v4, v6, v7, and v9 was performed on formalin-fixed, paraffin-embedded endocervical specimens. Seventeen cases of adenocarcinoma in situ (AIS) and 22 cases of invasive adenocarcinoma of the endocervix were included in this study, and the immunoreactivity was compared with that of normal endocervical epithelium.Results. (1) In the normal endocervical mucosa, immunoreactivity for CD44s and the splice variants was lacking or was confined to only the basal portion of the glandular epithelium along the basement membrane; (2) CD44s was diffusely expressed along the entire cytoplasmic membrane, including the luminal surface of the tumorous glands in 94% of AIS and 95% of invasive adenocarcinomas; (3) a significantly stronger expression of CD44s was observed in invasive adenocarcinomas than in AIS; (4) in contrast to all other splice variants, CD44v9 demonstrated an increased expression in nearly all in situ and invasive lesions compared to the normal tissue; (5) CD44v4 and v6 were expressed only in a small proportion of invasive adenocarcinomas and were near totally absent in the in situ lesions; and (6) CD44 v7 was totally absent in all normal, in situ, and invasive lesions studied.Conclusions. It appears that neoplastic transformation of endocervical epithelium is associated with qualitative and quantitative changes in the expression of CD44 standard molecule and some CD44 splice variants.

Altered expression of CD44 in human prostate cancer during progression.

There is a great need for markers that distinguish slowly progressive from rapidly progressive prostate cancers in paraffin-embedded tissues. CD44, an adhesion molecule that has been useful for the prediction of prognosis in some other cancers, has not been described in prostate cancer. The expression of CD44 was investigated with the monoclonal antibody GKW.A3 in prostate cancer in formalin-fixed, paraffin-embedded tissue sections of (1) whole prostates from 50 patients with 74 prostate cancers; and (2) lymph node metastases from 14 patients. Sixty percent of primary prostate cancers expressed CD44 moderately to strongly. No metastases expressed CD44 moderately to strongly; only 14% of metastases expressed even low levels of immunohistochemically detectable CD44. There is a difference between primary and metastatic prostate cancer (P <.0006) in the expression of CD44 and an inverse correlation (P <.05) between histological differentiation (Gleason grade) and the expression of CD44. The magnitude of the differential expression of CD44 in primary and metastatic prostate cancers suggests it should be investigated as an indicator of prognosis in a large prospective study.

EXPRESSION OF CD44 SPLICE VARIANTS IN BLADDER CANCER

Recently, it was noted that CD44 participates in a wide variety of cell-cell or cell-matrix interactions including tumor metastasis and the altered expression of CD44 splice variants is helpful in the diagnosis of colon and breast cancer. The purpose of the study was to investigate altered expression of CD44 in bladder cancer. Thirty-three surgical specimens of 22 patients and seven bladder cancer cell-lines were analyzed by various methods including RT-PCR-Southern blotting. Northern blotting, and flow-cytometric analysis. In RT-PCR analysis, the hematopoietic variant and numerous additional variants were detected in all cell-lines and almost all surgical specimens. In three out of seven cell-lines of bladder cancer (42.9%), especially numerous larger bands (ladder pattern) were detected using RT-PCR. These three cell-lines expressed a smaller quantity of CD44 mRNAs and CD44 molecules than the other four cell-lines. In eighteen out of 22 (81.8%) bladder cancer specimens, we detected larger variants that exceed 1500 base pairs, compared with the detection in four out of eleven (36.4%) visually normal mucosa specimens (P < 0.05). However, there was no correlation between the expression of the larger variants and clinicopathological features. The quantitative and qualitative change of CD44 variants were demonstrated in bladder cancer.

High‐level Expression of the CD44 Variant Sharing Exon v10 in Renal Cancer

To examine whether renal cell carcinoma displays altered CD44 expression we performed reverse transcription‐polymerase chain reaction (RT‐PCR) analysis of CD44 in 38 specimens from renal cancer, normal kidney and metastases of 19 patients and 6 renal cancer cell lines. To detect the CD44 variants, we utilized the RT‐PCR Southern blot method. One out of 19 (5.3%) renal cancer specimens expressed a larger molecular weight band than 1 kb by RT‐PCR analysis, in contrast to previous findings in colon and breast cancer. The band patterns in RT‐PCR were different in 14/17 (82.4%) cases between normal kidney and tumors, and a band of about 700 bp was especially marked in 12/17 (70.6%) tumor specimens and 4/6 (66.7%) cell lines. By cloning and sequencing of the 700 bp band, we found that this variant is identical to the CD44 variant sharing only exon v10. Examination by Northern blot analysis has revealed that all tumors express a higher level of CD44 mRNA than paired normal kidneys. These findings suggested that the CD44 variants sharing exon v10 play some role in renal cancer.

Expression of CD44R1 adhesion molecule in colon carcinomas and metastases

CD44 is a cell surface adhesion molecule postulated to control lymphocyte recirculation by facilitating entry into lymphoid tissue. Tumour cells transfected to overexpress the epithelial variant CD44R1 readily gain access to lymph nodes and distant metastatic sites in animal models, possibly by mimicking circulating lymphocytes.. To investigate if human tumours display altered CD44 expression we performed reverse transcriptase a polymerase chain reaction (PCR) analysis of CD44 in 49 specimens from normal colonic mucosa, primary colon and rectal tumours, normal liver, and metastases of 20 patients. The haematopoietic variant CD44H was the principal isoform amplified in all of the specimens, However, 12/14 primary tumours and 16/16 metastatic tumours expressed CD44R1, compared with only 2 of 13 normal mucosa specimens. This increase in CD44R1 relative to CD44H expressed by human colon carcinoma cells may increase their metastatic potential. Moreover, the relative increase in PCR amplification of CD44R1 compared with that of CD44H may provide a sensitive method for detecting primary and metastatic colon carcinoma cells in small biopsy specimens.